Hitherto, the diabetes is known as a disease that is caused by a morbid abnormal elevation of the blood glucose level due to the defects of the glucose metabolism, resulting in various complications.
In particular, the type 2 diabetes caused by a decreased insulin secretion and a reduced susceptibility to insulin is considered as accounting for a majority of total patients with diabetes in this country. And it is a complicated multifactorial disease that develops and advances by a variety of environmental factors including overeating, dietary composition, stress, lack of exercise, and the like, in addition to the genetic causes.
To date, therefore, many researchers have conducted research on type 2 diabetes using non-human mammalian animals which are considered to demonstrate pathological conditions of the type 2 diabetes.
As such non-human mammalian animals, there may be mentioned, for example, ob/ob mice or db/db mice, discovered by Jackson Research Laboratory, U.S.
These mice may cause a decrease in the energy consumption in addition to an increase in the energy intake due to overeating, and demonstrate phenotypes including, for example, high blood glucose, hyperinsulinemia, insulin resistance, a weight increase in the white adipocytes, and so on.
In 1994, the corresponding disease gene of the ob/ob mouse was identified by positional cloning and designated as “leptin” (see, for example, Non-Patent Literature Document #1). And, in 1995, the gene for leptin receptor was cloned and revealed as the disease gene for the db/db mouse (see, for example, Non-Patent Literature Document #2). At the present time, both of these mice have been used extensively as animal models for diabetes and obesity in biomedical research including the physiological and pharmacological functions of leptin.
Research on applications of animals developed by these genetic engineering techniques are expected to help not only in making a detailed clarification of a molecular function of the secretion and action of insulin, but also in making it feasible to clarify the pathological conditions of the type 2 diabetes as a multifactorial disease by the load of several genetic factors and environmental factors. Further, this research field is considered as indispensable to an application to development of new treatment methods including gene therapy, regenerative therapy and therapeutic agents as well as to a clarification of the onset and the pathological conditions of the diabetes.